Promitil® (Overview) 1
LipoMedix Pharmaceutical Inc. has developed Promitil®, a proprietary formulation of a lipid-based pro-drug of MMC (MLP) which enables efficient delivery and release of active MMC to tumors in vivo.
This novel formulation lowers the toxicity of free MMC and enhances anti-tumor activity against tumors including multi-drug resistant cancers. Promitil® has a long blood circulation lifetime and is capable of retaining the entrapped pro-drug for a desired time, yet able to release the drug on demand.
Our lead product, Promitil® shows a superior antitumor effect than many standard forms of chemotherapy (Cisplatin, Irinotecan, Gemcitabine, Doxorubicin) in tumor models.
The technology is derived from a unique lipid-based Prodrug of Mitomycin-C (MMC: 2,3- (distearoyloxy)propane-1-dithio-4Vbenzyloxycarbonyl) specially designed for liposome formulation.
The lipid anchor, responsible for the attachment of the MLP, was especially designed to provide strong, stable and prolonged association with liposomal membranes. The thiobenzyl bridge between the lipophilic anchor and the MMC moiety is cleaved by reducing agents which are abundant in tumors thus releasing active MMC which will then attack and kill tumor cells. Thus, MLP was rationally designed to allow optimal entrapment in liposomes, circulation in a non-active, non-toxic form and release of active drug after liposomes have lodged into target tissues
Promitil® is being developed as an anticancer agent that offers a reduced toxicity profile relative to free MMC, and shows activity against multi-drug resistant tumors. In tumor models in which free MMC was unable to achieve a dose level with therapeutic efficacy against multi-drug resistant tumors, Promitil® demonstrated significant therapeutic efficacy leading to significant extension of animal survival.
Promitil® is expected to induce a similar attenuation of toxicity in humans, with direct clinical benefit to cancer patients.
Therapeutic Effect of Promitil in mouse MDR tumor model (M109R). DOXIL™, 10 mg/kg q7dx2; PL-MLP, 35 mg/kg (10 mg/kg MMC=equivalents) q7dx2
The Pegylated Liposomal Formulation of Mitomycin-C Lipid-based Prodrug (Promitil®) is a sophisticated therapeutic and delivery system that has several unique advantages:
- Formulation of a prodrug of mitomycin-C (an already well- established drug) that is more efficacious than the drug in free form and has a reduced systemic toxicity
- Unique mode of action
- Extended circulation time and shelf life
- Inhibits a range of cancer types
- Greater efficacy against multidrug resistant tumors, surpassing that of Doxil and Doxorubicin in tumor models
- Uses a well-established pegylated liposomal delivery system
- Potential enhancement activity in combination with other anticancer agents
